This program project grant considers certain features of aging cells and tissues. Studies are in progress on the state of certain mixed function oxidative systems (MFO) in aging cells; in particular, we are examining prolyl hydroxylase and MFO's involved in the metabolism of certain drugs. We are also investigating the decline of some x-chromosome linked enzyme processes with cell population doubling in vitro and relating this to the appearance of certain maturity onset disorders. Examination of the status of the "LDL" receptors in aging cells also indicates a decline of receptors with increasing population doubling. Our observation of a vitamin K-dependent system in bone and the presence of a protein, osteocalcin, which contains gamma-carboxyglutamic acid has suggested a role of vitamin K in the development of normal bone. Studies in progress suggest that defects in this vitamin K system may contribute to the development of senile and postmenopausal osteoporosis. In general, this program consists of several projects which examine a variety of cell and tissue "age" dependent properties which are of considerable importance in geriatric medicine.